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Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death
eLife ( IF 6.4 ) Pub Date : 2018-03-20 , DOI: 10.7554/elife.30134
Laurelle Jackson 1, 2 , Jessica Hunter 1, 2 , Sandile Cele 1 , Isabella Markham Ferreira 1, 2 , Andrew C Young 1, 3 , Farina Karim 1 , Rajhmun Madansein 4, 5 , Kaylesh J Dullabh 4 , Chih-Yuan Chen 4 , Noel J Buckels 4 , Yashica Ganga 1 , Khadija Khan 1 , Mikael Boulle 1 , Gila Lustig 1 , Richard A Neher 6, 7 , Alex Sigal 1, 2, 8
Affiliation  

HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high.

中文翻译:

HIV感染的不完全抑制通过减少细胞死亡导致更多HIV感染的淋巴结细胞

据报道,HIV 在体外和淋巴结感染模型中具有细胞毒性。使用计算方法,我们发现对每个细胞多个病毒粒子的传播的部分抑制可能导致活感染细胞数量的增加。如果抑制后病毒 DNA 拷贝数保持在 1 以上,则消除多余的病毒拷贝会减少细胞死亡。使用细胞系,当感染被抗逆转录病毒依法韦仑或中和抗体部分抑制时,我们观察到活感染细胞的数量增加。然后我们以淋巴结中报道的浓度使用依法韦仑来抑制部分抗性 HIV 突变体的淋巴结感染。我们观察到更多活的感染淋巴结细胞,但与没有药物相比,每个细胞的 HIV DNA 拷贝更少。因此,与直觉相反,
更新日期:2018-03-20
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